1. Field
Methods and compositions for cancer chemoprevention. In particular, methods and compositions that inhibit growth and/or development of tumors.
2. Background
Prostaglandins are members of a group of lipid compounds derived enzymatically from fatty acids and are found in nearly all tissues and organs. Prostaglandin D2 (PGD2) represents one group of prostaglandins, which are produced in the body by enzymes called prostaglandin D synthases.
Two enzymes account for PGD2 production in the body. One enzyme is the brain type, which occurs in the nervous system, epididymis, and heart. It resembles lipophilic ligand-carrier proteins and is called lipocalin-type prostaglandin D synthase (L-PGDS). The enzyme is a β-barrel monomer that undergoes cleavage of a signal peptide, glycosylation, phosphorylation, and cysteine oxidation. Mice lacking L-PGDS do not have the normal pain response (allodynia) after infusion of prostaglandin E2 (PGE2) into spinal fluid.
The other enzyme is known as hematopoietic prostaglandin D synthase (H-PGDS). This enzyme was first prepared from rat spleen and later identified in the gut and other organs. H-PGDS is a glutathione transferase (sigma type), on the basis of its amino acid sequence and use of glutathione as a cofactor. The enzyme is a homodimer and folds like other glutathione transferases.
When originally discovered, D series prostaglandins were viewed as by-products of prostaglandin E synthesis. However, PGD2 is now known as a regulator of sleep, platelet aggregation, inflammation, smooth muscle contraction, and bronchoconstriction.